Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is a neurological disorder characterized by an irresistible urge to move one's body to stop uncomfortable or odd sensations. It most commonly affects the legs, but can affect the arms, torso, and even phantom limbs. RLS sensations range from pain or an aching in the muscles, to “an itch you can't scratch,” an unpleasant “tickle that won't stop,” or even a “crawling” feeling. The sensations typically begin or intensify during quiet wakefulness, such as when relaxing, reading, studying, or trying to sleep. For example, sitting or lying down (e.g., reading, plane ride, watching TV) can trigger the sensations and urge to move. These symptoms of RLS can make sleeping difficult for many patients and a recent poll shows the presence of significant daytime difficulties resulting from this condition. Additionally, most individuals with RLS suffer from periodic limb movement disorder (PLMD), which is an objective physiologic marker of the disorder and is associated with sleep disruption.
Movement usually brings immediate relief, although temporary and partial. Continuous, fast up-and-down movements of the leg, and/or rapidly moving the legs toward then away from each other, may keep sensations at bay without having to walk. The sensations—and the need to move—may return immediately after ceasing movement or at a later time. RLS may start at any age, including childhood, and is a progressive disease for most individuals.
Primary RLS is considered idiopathic or with no known cause. Primary RLS usually begins slowly, before approximately 40-45 years of age and may disappear for months or even years. It is often progressive and gets worse with age. RLS in children is often misdiagnosed as growing pains. Secondary RLS often has a sudden onset after age 40, and may occur daily from the beginning. It is most associated with specific medical conditions or the use of certain drugs.
Treatment is often with levodopa or a dopamine agonist. These hypotheses are based on the observation that iron and levodopa, a pro-drug of dopamine that can cross the blood-brain barrier and is metabolized in the brain into dopamine (as well as other mono-amine neurotransmitters of the catecholamine class) can be used to treat RLS, levodopa being a medicine for treating hypo-dopaminergic (low dopamine) conditions such as Parkinson's disease.
RLS drug therapy is not curative and has side effects such as nausea, dizziness, hallucinations, orthostatic hypotension, or daytime sleep attacks. There are, however, issues with the use of dopamine agonists including augmentation. This is a medical condition in which the drug itself causes symptoms to increase in severity and/or occur earlier in the day. Dopamine agonists may also cause rebound, when symptoms increase as the drug wears off. In many cases, the longer dopamine agonists are used the higher the risk of augmentation and rebound as well as the severity of the symptoms. A recent study has indicated that dopamine agonists used in restless leg syndrome may lead to an increase in compulsive gambling.
Thus, there is a need for more effective treatment of the RLS without the undesirable side effects of drugs currently used for RLS treatment.